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A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct. 胆管 1 型和 2 型导管内乳头状肿瘤综述。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI: 10.1007/s11596-024-2863-5
Xia-Hui Huang, Tian-Xiang Chen, Hong-Liang Liu, Ming-Wen Huang

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

胆管导管内乳头状瘤(IPNB)是一种异质性疾病,与胰腺导管内乳头状粘液瘤相似。自2010年起,这类病变被认定为胆道三大癌前病变之一。2018年,日本和韩国病理学家达成共识,将IPNB分为l型和2型IPNB。IPNB在东亚男性患者中发病率较高,与胆石症、血吸虫病等疾病密切相关。从分子遗传学角度看,IPNBs 表现出早期遗传变异,1 型和 2 型 IPNBs 的肿瘤发生可能涉及不同的分子途径。IPNBs 的组织学亚型包括胃亚型、肠亚型、胰胆亚型或肿瘤细胞亚型,但 1 型 IPNBs 通常比 2 型 IPNBs 表现出更规则、组织更有序的组织学特征,并且更常见于肝内胆管,具有丰富的粘蛋白。由于这些病变的罕见性以及缺乏特定的临床和实验室特征,影像学检查对 IPNB 的术前诊断至关重要,局部胆管扩张和沿胆管生长是主要的影像学特征。手术切除仍是 IPNB 的最佳治疗方法,但胆管边缘阴性和切除肝门淋巴结可显著提高 IPNB 患者的术后生存率。
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引用次数: 0
Characteristics and Risk Factors for Pediatric Sepsis. 小儿败血症的特征和风险因素。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI: 10.1007/s11596-024-2870-6
Yong-Bing Zhu, Tong-Lin Liu, Qi Dai, Shu-Fan Liu, Peng Xiong, Hao Huang, Yi Yuan, Tian-Nan Zhang, Yu Chen

Objective: Sepsis is considered a major cause of health loss in children and had high mortality and morbidity. Currently, there is no reliable model for predicting the prognosis of pediatric patients with sepsis. This study aimed to analyze the clinical characteristics of sepsis in children and assess the risk factors associated with poor prognosis in pediatric sepsis patients to identify timely interventions and improve their outcomes.

Methods: This study analyzed the clinical indicators and laboratory results of septic patients hospitalized in the Pediatric Intensive Care Unit of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, China, from January 1, 2019, to December 31, 2021. Risk factors for sepsis were identified by logistic regression analyses.

Results: A total of 355 children with sepsis were enrolled, with 333 children (93.8%) in the good prognosis group, and 22 children (6.2%) in the poor prognosis group. Among them, there were 255 patients (71.8%) in the sepsis group, and 100 patients (28.2%) in the severe sepsis group. The length of hospital stay in the poor prognosis group was longer than that in the good prognosis group (P<0.01). The levels of interleukin 1β (IL-1β) in the poor prognosis group were higher than those in the good prognosis group (P>0.05), and the platelet (PLT), albumin (ALB), and hemoglobin (Hb) levels were lower in the poor prognosis group (P<0.01). The IL-8 levels in the severe sepsis group were higher than those in the sepsis group (P<0.05). Multiple logistic regression analysis suggested that lower Hb levels, ALB levels, peak PLT counts, and higher IL-1β levels were independent risk factors for poor prognosis in children with sepsis.

Conclusion: Lower Hb, ALB, and PLT counts and elevated IL-1β are independent risk factors for poor prognosis in children with sepsis.

目的:败血症被认为是导致儿童健康受损的主要原因,死亡率和发病率都很高。目前,还没有可靠的模型来预测儿童败血症患者的预后。本研究旨在分析儿童败血症的临床特征,并评估与小儿败血症患者预后不良相关的风险因素,以确定及时的干预措施并改善其预后:本研究分析了2019年1月1日至2021年12月31日在中国华中科技大学同济医学院附属同济医院儿科重症监护室住院的败血症患者的临床指标和实验室结果。通过逻辑回归分析确定了败血症的风险因素:共纳入355名败血症患儿,其中预后良好组333名(93.8%),预后不良组22名(6.2%)。其中,脓毒症组有 255 名患儿(71.8%),严重脓毒症组有 100 名患儿(28.2%)。预后不良组的住院时间长于预后良好组(P0.05),预后不良组的血小板(PLT)、白蛋白(ALB)和血红蛋白(Hb)水平较低(PC结论:Hb、ALB和PLT计数降低以及IL-1β升高是败血症患儿预后不良的独立危险因素。
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引用次数: 0
Effect of Jianpi Shengxue Tablet on Iron Metabolism and Nutritional Status in Patients with Renal Anemia: A Prospective, Randomized, Open, Parallel Controlled and Multicenter Clinical Study. 健皮生血片对肾性贫血患者铁代谢和营养状况的影响:一项前瞻性、随机、开放、平行对照和多中心临床研究。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-05-28 DOI: 10.1007/s11596-024-2867-1
Juan Yang, Meng-Yuan Liang, Yu Li, Hao Zhang, Wei Li, Jing Lv, Li-Ping Dong, Jing-Song Jin, Cheng Yang, Qing-Hong Zhang, Li Long, Rong Zou, Yi Gao, Dan Song, Chun-Qin Pan, Ying Yao, Xiao-Lin Zhan, Xiao-Hui Wang

Objective: This study aimed to analyze the clinical efficacy of the Jianpi Shengxue tablet for treating renal anemia.

Methods: A total of 200 patients with renal anemia from December 2020 to December 2022 were enrolled and randomly divided into two groups. Patients in the control group were treated with polysaccharide-iron complex, and those in the experimental group were administered Jianpi Shengxue tablet. After 8 weeks of continuous treatment, the therapeutic outcomes regarding anemia were compared between the two groups.

Results: After treatment, the red blood cell (RBC) count, hematocrit (HCT), reticulocyte percentage (RET), ferritin (SF), serum iron (SI), transferrin saturation (TSAT), and serum albumin (ALB) all increased (P<0.01), and the clinical symptom score and total iron binding capacity decreased (P<0.01) in the experimental group. Moreover, the improvements in RBC, HCT, RET, SF, SI, TAST, ALB, and clinical symptoms (fatigue, anorexia, dull skin complexion, numbness of hands and feet) in the experimental group were significantly greater than those in the control group (P<0.05). The total effective rate for treating renal anemia was significantly higher in the experimental group than in the control group (P<0.01).

Conclusion: The Jianpi Shengxue tablet demonstrates efficacy in treating renal anemia, leading to significant improvements in the laboratory examination results and clinical symptoms of patients with renal anemia.

目的:分析健皮生血片治疗肾性贫血的临床疗效:本研究旨在分析健皮生血片治疗肾性贫血的临床疗效:方法:选取2020年12月至2022年12月期间的肾性贫血患者共200例,随机分为两组。对照组患者接受多糖铁复合物治疗,实验组患者服用健皮生血片。连续治疗 8 周后,比较两组患者贫血的治疗效果:结果:治疗后,两组患者的红细胞计数(RBC)、血细胞比容(HCT)、网织红细胞百分比(RET)、铁蛋白(SF)、血清铁(SI)、转铁蛋白饱和度(TSAT)和血清白蛋白(ALB)均有所增加(PC结论:健皮生血片对贫血的治疗效果显著:健皮生血片对治疗肾性贫血有显著疗效,能明显改善肾性贫血患者的实验室检查结果和临床症状。
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引用次数: 0
Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial. 用于检测结直肠腺瘤的标准清晰度白光、高清晰度白光与窄带成像内窥镜:多中心随机对照试验。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-06-06 DOI: 10.1007/s11596-024-2882-2
Chang-Wei Duan, Hui-Hong Zhai, Hui Xie, Xian-Zong Ma, Dong-Liang Yu, Lang Yang, Xin Wang, Yu-Fen Tang, Jie Zhang, Hui Su, Jian-Qiu Sheng, Jun-Feng Xu, Peng Jin

Objective: This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population.

Methods: This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression.

Results: Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80).

Conclusion: HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

研究目的本研究旨在比较标准清晰度白光内镜(SD-WL)、高清晰度白光内镜(HD-WL)和高清晰度窄带成像(HD-NBI)在中国人群中检测结直肠病变的效果:这是一项多中心、单盲、随机对照试验,采用非劣效性设计。2017年7月至2020年12月,接受内镜体检、筛查和监测的患者入组。主要结果指标是腺瘤检出率(ADR),即至少检出一个腺瘤的患者比例。使用单变量和多变量逻辑回归评估了检测到腺瘤的相关因素:在 653 名符合条件的登记患者中,对 596 名患者的数据进行了分析。SD-WL组的ADR为34.5%,HD-WL组为33.5%,HD-NBI组为37.5%(P=0.72)。三组的晚期肿瘤检出率(ANDRs)分别为17.1%、15.5%和10.4%(P=0.17)。SD组与HD组在ADR或ANDR方面无明显差异(ADR:分别为34.5% vs. 35.6%,P=0.79;ANDR:分别为17.1% vs. 13.0%,P=0.16)。在 HD-WL 组和 HD-NBI 组之间也观察到类似的结果(ADR:33.5% 对 37.7%,P=0.45;ANDR:15.5% 对 10.4%,P=0.18)。在单变量和多变量逻辑回归分析中,与SD-WL相比,HD-WL和HD-NBI在腺瘤总检出率方面均无显著差异(HD-WL:OR 0.91,P=0.69;HD-NBI:OR 1.15,P=0.80):结论:在中国门诊患者中,HD-NBI和HD-WL的腺瘤总体检出率与SD-WL相当。结论:在中国门诊患者中,HD-NBI 和 HD-WL 的腺瘤总体检出率与 SD-WL 相当,可以认为 HD-NBI 或 HD-WL 并不优于 SD-WL,但未来可能需要更有效的指导来指导不同内镜方法的选择。我们的研究结论可能有助于有效分配和利用有限的结肠镜检查资源,尤其是先进的成像技术。
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引用次数: 0
The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders. 脂肪组织衍生的外泌体在慢性代谢紊乱中的作用
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-06-20 DOI: 10.1007/s11596-024-2902-2
Rui He, Yong Chen

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases, such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles (EVs) that play a role in the regulation of whole-body metabolism. Exosomes are a subtype of EVs, and accumulating evidence indicates that adipose tissue exosomes (AT Exos) mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms. However, the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated. In this review, we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders. Moreover, we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

肥胖者体内过多的脂肪沉积会诱发代谢性疾病,如 2 型糖尿病(T2DM)、心血管疾病和非酒精性脂肪肝(NAFLD)。脂肪组织不仅是能量储存的主要形式,也是一个内分泌器官,不仅能分泌脂肪细胞因子,还能释放出许多细胞外小泡(EVs),在调节全身代谢中发挥作用。外泌体是EVs的一种亚型,越来越多的证据表明,脂肪组织外泌体(AT Exos)通过旁分泌或内分泌机制转移到目标细胞或组织,从而介导脂肪组织与多个器官之间的串联。然而,脂肪组织外泌体在与代谢器官串联中的作用仍有待全面阐明。在这篇综述中,我们总结了 AT Exos 在调节代谢紊乱中的作用的最新研究进展。此外,我们还讨论了AT Exos作为生物标记物在代谢性疾病中的潜在作用及其临床应用。
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引用次数: 0
Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study. 人参皂苷 Rb1 对脑部微血管内皮细胞的保护作用中氧化应激、自噬和细胞凋亡之间的相互影响:计算与实验的混合研究。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-06-10 DOI: 10.1007/s11596-024-2858-2
Yi-Miao Luo, Shu-Sen Liu, Ming Zhao, Wei Wei, Jiu-Xiu Yao, Jia-Hui Sun, Yu Cao, Hao Li

Objective: Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs.

Methods: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings.

Results: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage.

Conclusion: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.

目的:研究发现,脑微血管内皮细胞(BMECs)在缺血性脑卒中(IS)中会从通常的非活性状态转变为活性状态,并导致神经元损伤。人参皂苷 Rb1(GRb1)是一种从药用植物中提取的成分,因其对缺血性中风的药理作用而闻名,但其对 BMECs 的保护作用还有待探索。本研究旨在探讨 GRb1 对 BMECs 的潜在保护作用:方法:建立体外氧-葡萄糖剥夺/再灌注(OGD/R)模型来模拟缺血再灌注(I/R)损伤。利用人类自噬数据库和多种生物信息学工具分析了大量 RNA 序列数据,包括基因组富集分析(GSEA)、基因本体(GO)分类和富集分析、京都基因组百科全书(KEGG)通路分析、蛋白质相互作用网络分析和分子对接。为确保研究结果的可靠性,还进行了实验验证:结果:Rb1对遭受OGD/R损伤的BMEC具有保护作用。结果:Rb1 对遭受 OGD/R 损伤的 BMEC 有保护作用,特别是,研究发现 GRb1 可调节 BMEC 中氧化应激、细胞凋亡和自噬之间的相互作用。研究发现了一些关键靶点,如序列组1(SQSTM1/p62)、自噬相关5(ATG5)和低氧诱导因子1-α(HIF-1α),这些靶点在介导GRb1对IS诱导的损伤的保护作用中发挥了潜在作用:结论:GRbl通过影响氧化应激、细胞凋亡和自噬,保护BMECs免受OGD/R损伤。SQSTM1/p62、ATG5和HIF-1α被确定为有希望的靶点,这进一步支持了GRb1作为IS治疗剂的潜力,为今后研究其在IS治疗中的机制和应用奠定了基础。
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引用次数: 0
Transforming Adolescent Smiles: Correcting Skeletal Mandibular Retrusion and Bimaxillary Protrusion with Clear Aligners. 改变青少年的笑容:使用透明矫治器矫正下颌骨后突和双颌前突。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI: 10.1007/s11596-024-2856-4
Wen-Jie Fan, Jia-Qi Zhang, Jia-Qi Zhan, Li Hu, Li-Li Chen

Maxillary protrusion combined with mandibular retraction is a highly prevalent but extremely complex maxillofacial deformity that can have a serious negative impact on patients' facial aesthetics and mental health. The traditional orthodontic treatment strategy often involves extracting 4 first premolars and conventional fixed techniques, combined with mini-implant screws, to retract the anterior teeth and improve facial protrusion. In recent years, an invisible orthodontic technique, without brackets, has become increasingly popular. However, while an invisible aligner has been used in some cases with reasonable results, there remain significant challenges in achieving a perfect outcome. This case report presents an adolescent patient with bimaxillary protrusion and mandibular retrognathia. Based on the characteristics of the invisible aligners and the growth characteristics of the adolescent's teeth and jawbone, we designed precise three-dimensional tooth movement and corresponding resistance/over-correction for each tooth, while utilizing the patient's jawbone growth potential to promote rapid development of the mandible, accurately and efficiently correcting bimaxillary protrusion and skeletal mandibular retrognathia. The patient's facial aesthetics, especially the lateral morphology, have been greatly improved, and various aesthetic indicators have also shown significant changes, and to the patient's great benefit, invasive mini-implant screws were not used during the treatment. This case highlights the advantages of using invisible aligners in adolescent maxillary protrusion combined with mandibular retraction patients. Furthermore, comprehensive and accurate design combined with good application of growth potential can also enable invisible orthodontic technology to achieve perfect treatment effects in tooth extractions, providing clinical guidance for orthodontists.

上颌前突合并下颌后缩是一种非常普遍但极其复杂的颌面部畸形,会对患者的面部美观和心理健康造成严重的负面影响。传统的正畸治疗策略通常包括拔除 4 颗第一前磨牙和传统的固定技术,并结合微型种植螺钉来牵引前牙和改善面部前突。近年来,无托槽的隐形正畸技术越来越受欢迎。然而,虽然隐形矫治器在一些病例中的应用取得了合理的效果,但要实现完美的矫治效果仍面临着巨大的挑战。本病例报告介绍了一位患有双颌前突和下颌后缩的青少年患者。我们根据隐形矫治器的特性以及该青少年牙齿和颌骨的生长特点,为每颗牙齿设计了精确的三维牙齿移动和相应的阻力/过度矫正,同时利用患者颌骨的生长潜力促进下颌骨的快速发育,准确有效地矫正了双颌前突和下颌后缩。患者的面部美观,尤其是侧面形态得到了极大改善,各项美学指标也发生了显著变化,而且治疗过程中没有使用侵入性微型种植螺钉,这让患者受益匪浅。该病例凸显了在青少年上颌前突合并下颌后缩患者中使用隐形矫治器的优势。此外,全面准确的设计结合良好的生长势应用,也能使隐形矫治技术在拔牙治疗中达到完美的治疗效果,为正畸医生提供临床指导。
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引用次数: 0
Comment on: Clinical Characteristics, Diagnosis, and Treatments for COVID-19. 评论COVID-19的临床特征、诊断和治疗。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-05-29 DOI: 10.1007/s11596-024-2897-8
Ying Wen, Xin-Dan Hu
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引用次数: 0
Immunomodulation of Proton-activated G Protein-coupled Receptors in Inflammation. 质子激活的 G 蛋白偶联受体在炎症中的免疫调节作用。
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI: 10.1007/s11596-024-2872-4
Min-Shan Li, Xiang-Hong Wang, Heng Wang

Proton-activated G protein-coupled receptors (GPCRs), initially discovered by Ludwig in 2003, are widely distributed in various tissues. These receptors have been found to modulate the immune system in several inflammatory diseases, including inflammatory bowel disease, atopic dermatitis, and asthma. Proton-activated GPCRs belong to the G protein-coupled receptor family and can detect alternations in extracellular pH. This detection triggers downstream signaling pathways within the cells, ultimately influencing the function of immune cells. In this review, we specifically focused on investigating the immune response of proton-activated GPCRs under inflammatory conditions.

质子激活的 G 蛋白偶联受体(GPCR)最初由路德维希于 2003 年发现,广泛分布于各种组织中。研究发现,这些受体在炎症性肠病、特应性皮炎和哮喘等多种炎症性疾病中调节免疫系统。质子激活型 GPCR 属于 G 蛋白偶联受体家族,可以检测细胞外 pH 值的变化。这种检测会触发细胞内的下游信号通路,最终影响免疫细胞的功能。在这篇综述中,我们特别侧重于研究质子激活的 GPCR 在炎症条件下的免疫反应。
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引用次数: 0
TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway. TRPC6基因敲除可通过PI3K/AKT/GSK3B途径缓解肾脏纤维化
IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Pub Date : 2024-06-01 Epub Date: 2024-05-15 DOI: 10.1007/s11596-024-2869-z
An-Bang Sun, Fang-Hua Li, Lin Zhu, Xi-Xi Zeng, Min Zhu, Qing-Hua Lei, Yan-Hong Liao

Objective: Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage. Notably, the knockout of transient receptor potential channel 6 (TRPC6) has shown promise in alleviating renal fibrosis. However, the regulatory impact of TRPC6 on renal fibrosis remains unclear.

Methods: In vivo, TRPC6 knockout (TRPC6-/-) mice and age-matched 129 SvEv (WT) mice underwent unilateral renal ischemia-reperfusion (uIR) injury surgery on the left renal pedicle or sham operation. Kidneys and serum were collected on days 7, 14, 21, and 28 after euthanasia. In vitro, primary tubular epithelial cells (PTECs) were isolated from TRPC6-/- and WT mice, followed by treatment with transforming growth factor β1 (TGFβ1) for 72 h. The anti-fibrotic effect of TRPC6-/- and the underlying mechanisms were assessed through hematoxylin-eosin staining, Masson staining, immunostaining, qRT-PCR, and Western blotting.

Results: Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ1. TRPC6-/- alleviated renal fibrosis by reducing the expression of fibrotic markers (Col-1, α-SMA, and vimentin), as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro. Additionally, we found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) signaling pathway, a pivotal player in renal fibrosis, was down-regulated following TRPC6 deletion.

Conclusion: These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3β pathway. Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

目的:肾脏纤维化是各种急性和慢性肾脏损伤的最终途径。值得注意的是,敲除瞬时受体电位通道 6(TRPC6)有望缓解肾脏纤维化。然而,TRPC6对肾脏纤维化的调节作用仍不清楚:在体内,TRPC6基因敲除(TRPC6-/-)小鼠和年龄匹配的129 SvEv(WT)小鼠接受了左肾梗单侧肾缺血再灌注(uIR)损伤手术或假手术。安乐死后第 7、14、21 和 28 天收集肾脏和血清。通过苏木精-伊红染色、Masson染色、免疫染色、qRT-PCR和Western印迹法评估了TRPC6-/-的抗纤维化作用及其机制:结果:在uIR小鼠和经TGFβ1处理的PTECs中观察到TRPC6表达增加。TRPC6-/-通过减少纤维化标志物(Col-1、α-SMA 和波形蛋白)的表达,以及减少体内和体外纤维化进展过程中 PTECs 的凋亡和炎症,缓解了肾脏纤维化。此外,我们还发现,在TRPC6缺失后,磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/糖原合成酶激酶3β(GSK3β)信号通路(肾脏纤维化的关键角色)被下调:这些结果表明,TRPC6的消减可通过下调PI3K/AKT/GSK3β通路抑制PTECs的凋亡和炎症,从而缓解肾脏纤维化。以TRPC6为靶点可能是预防慢性肾病的一种新型治疗策略。
{"title":"TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway.","authors":"An-Bang Sun, Fang-Hua Li, Lin Zhu, Xi-Xi Zeng, Min Zhu, Qing-Hua Lei, Yan-Hong Liao","doi":"10.1007/s11596-024-2869-z","DOIUrl":"10.1007/s11596-024-2869-z","url":null,"abstract":"<p><strong>Objective: </strong>Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage. Notably, the knockout of transient receptor potential channel 6 (TRPC6) has shown promise in alleviating renal fibrosis. However, the regulatory impact of TRPC6 on renal fibrosis remains unclear.</p><p><strong>Methods: </strong>In vivo, TRPC6 knockout (TRPC6<sup>-/-</sup>) mice and age-matched 129 SvEv (WT) mice underwent unilateral renal ischemia-reperfusion (uIR) injury surgery on the left renal pedicle or sham operation. Kidneys and serum were collected on days 7, 14, 21, and 28 after euthanasia. In vitro, primary tubular epithelial cells (PTECs) were isolated from TRPC6<sup>-/-</sup> and WT mice, followed by treatment with transforming growth factor β1 (TGFβ1) for 72 h. The anti-fibrotic effect of TRPC6<sup>-/-</sup> and the underlying mechanisms were assessed through hematoxylin-eosin staining, Masson staining, immunostaining, qRT-PCR, and Western blotting.</p><p><strong>Results: </strong>Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ1. TRPC6<sup>-/-</sup> alleviated renal fibrosis by reducing the expression of fibrotic markers (Col-1, α-SMA, and vimentin), as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro. Additionally, we found that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) signaling pathway, a pivotal player in renal fibrosis, was down-regulated following TRPC6 deletion.</p><p><strong>Conclusion: </strong>These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3β pathway. Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":"589-602"},"PeriodicalIF":2.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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